Biology subjects

Villa del Campo, C.

Publications and source records attributed to Villa del Campo, C..

2 recordsLinked to original sources

bioRxiv2020

Tissue-resident macrophages regulate lymphatic vessel growth and patterning in the developing heart

Macrophages are components of the innate immune system with key roles in tissue inflammation and repair. It is now evident that macrophages also support organogenesis, but few studies have characterized their identity, ontogeny and function during heart development. Here, we show that resident macrophages in the subepicardial compartment of the developing heart coincide with the emergence of new lymphatics and interact closely with the nascent lymphatic capillaries. Consequently, global macrophage-deficiency led to extensive vessel disruption with mutant hearts exhibiting shortened and mis-patterned lymphatics. The origin of cardiac macrophages was linked to the yolk sac and fetal liver. Moreover, Csf1r+ and Cx3cr1+ myeloid sub-lineages were found to play essential functions in the remodeling of the lymphatic endothelium. Mechanistically, macrophage hyaluronan was found to be required for lymphatic sprouting by mediating direct macrophage-lymphatic endothelial cell interactions. Together, these findings reveal insight into the role of macrophages as indispensable mediators of lymphatic growth during the development of the mammalian cardiac vasculature.Summary statement Tissue-resident macrophages are indispensable mediators of lymphatic vessel formation during heart development and function to remodel the vascular plexus.View Full Text

developmental biology↗

bioRxiv2018

Myc is dispensable for cardiac development in the mouse but can rescue Mycn-deficient hearts through functional replacement and cell competition

Myc is considered an essential transcription factor for heart development, but cardiac defects have only been studied in global Myc loss of function models. Here, we eliminated Myc by recombining a Myc floxed allele with the Nkx2.5Cre driver. We observed no anatomical, cellular or functional alterations in either fetuses or adult cardiac Myc-deficient mice. We re-examined Myc expression during development and found no expression in developing cardiomyocytes. In contrast, we confirmed that Mycn is essential for cardiomyocyte proliferation and cardiogenesis. Mosaic Myc overexpression in a Mycn-deficient background, shows that Myc can replace Mycn function, recovering heart development. We further show that this recovery involves the elimination of Mycn-deficient cells by Cell Competition. Our results indicate that Myc is dispensable during cardiogenesis and adult heart homeostasis and Mycn is exclusively responsible for cardiomyocyte proliferation during heart development. Nonetheless, our results show that Myc can functionally replace Mycn. We also show that cardiomyocytes compete according to their overall Myc+Mycn levels and that Cell Competition eliminates flawed cardiomyocytes, suggesting its relevance as a quality control mechanism in cardiac development.

developmental biology↗